Every year, millions of people suffer tissue loss or end-stage organ failure (see, e.g., Langer and Vacanti, Science 260:920–926, 1993). When possible, physicians treat this loss or failure by transplanting organs from one individual to another, performing surgical reconstruction, or using mechanical devices such as kidney dialyzers. Although these therapies have saved and improved countless lives, they are imperfect solutions. Transplantation is severely limited by critical donor shortages, which worsen every year, and surgical reconstruction can cause long-term problems. For example, colon cancers often develop after surgical treatment of incontinence that directs urine into the colon. Mechanical devices are inconvenient for the patient, and their performance to date cannot match that of an intact organ. Few, if any, of these treatments can restore the tissue lost or prevent progression of the underlying disorder.
An alternative to the measures described above is tissue engineering, an interdisciplinary science that applies engineering and physiological principles to the development of biological substitutes that maintain, improve, or restore tissue function (Tissue Engineering, R. Skalak and C. F. Fox, Eds., Alan R. Liss, New York, N.Y., 1988; Nerem, Ann. Biomed. Eng. 19:529, 1991). Three general strategies have been adopted for the creation of new tissue. The first employs isolated cells or cell substitutes. This approach avoids the complications of surgery, allows replacement of only those cells that supply the needed function, and permits manipulation of cells before they are administered to a patient. However, the cells do not always maintain their function in the recipient, and they can evoke an immune response that results in their destruction. The second approach employs tissue-inducing substances. For this approach to succeed, appropriate signal molecules, such as growth factors, must be purified and appropriately targeted to the affected tissue. The third approach employs cells placed on or within matrices. In closed systems, these cells are isolated from the body by a membrane that is permeable to nutrients and wastes, but impermeable to harmful agents such as antibodies and immune cells. Closed systems can be implanted or used as extra-corporeal devices. In open systems, cell-containing matrices are implanted and become incorporated into the body. The matrices are fashioned from natural materials such as collagen or from synthetic polymers. Immunological rejection may be prevented by immunosuppressive drugs or by the use of autologous cells.